Inhibition of ABCB1 Overcomes Cancer Stem Cell-like Properties and Acquired Resistance to MET Inhibitors in Non-Small Cell Lung Cancer

Molecular Cancer Therapeutics
Teppei SuganoAkihiko Gemma

Abstract

Patients with non-small cell lung cancer (NSCLC) EGFR mutations have shown a dramatic response to EGFR inhibitors (EGFR-TKI). EGFR T790M mutation and MET amplification have been recognized as major mechanisms of acquired resistance to EGFR-TKI. Therefore, MET inhibitors have recently been used in NSCLC patients in clinical trials. In this study, we tried to identify the mechanism of acquired resistance to MET inhibitors. We analyzed the antitumor effects of two MET inhibitors, PHA-665752 and crizotinib, in 10 NSCLC cell lines. EBC-1 cells with MET amplification were the only cells that were sensitive to both MET inhibitors. We established PHA-665752-resistant EBC-1 cells, namely EBC-1R cells. Activation of KRAS, EGFR, and FGFR2 signaling was observed in EBC-1R cells by FISH and receptor tyrosine kinase phosphorylation antibody arrays. EBC-1R cells also showed overexpression of ATP-binding cassette subfamily B member 1 (ABCB1) as well as phosphorylation of MET. EBC-1R cells grew as cell spheres that exhibited cancer stem cell-like (CSC) properties and epithelial-mesenchymal transition (EMT). The level of miR-138 that targeted ABCB1 was decreased in EBC-1R cells. ABCB1 siRNA and the ABCB1 inhibitor elacridar could reduce sphere n...Continue Reading

References

Nov 2, 2001·Nature·T ReyaI L Weissman
Dec 20, 2003·Nature Reviews. Molecular Cell Biology·Carmen BirchmeierGeorge F Vande Woude
Feb 25, 2005·The New England Journal of Medicine·Susumu KobayashiBalázs Halmos
Jun 18, 2005·Cell·Anton Berns
Feb 8, 2006·Proceedings of the National Academy of Sciences of the United States of America·Stefano VoliniaCarlo M Croce
Mar 7, 2006·Nature Reviews. Drug Discovery·Gergely SzakácsMichael M Gottesman
Oct 25, 2006·Nature Reviews. Cancer·George A Calin, Carlo M Croce
Jun 5, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Isa E L M KuppensJan H M Schellens
Aug 10, 2007·Journal of the National Cancer Institute·Masahiro SeikeCurtis C Harris
Dec 1, 2007·Cell Death and Differentiation·A EramoR De Maria
Mar 12, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jurjen S LagasAlfred H Schinkel
Jul 15, 2009·Proceedings of the National Academy of Sciences of the United States of America·Masahiro SeikeCurtis C Harris
Nov 10, 2009·Leukemia Research·Xiaohong ZhaoJigang Ruan
Jan 23, 2010·Nature Reviews. Cancer·Nicholas Turner, Richard Grose
Jan 27, 2010·Expert Opinion on Therapeutic Patents·John Porter
Apr 28, 2010·The Journal of Pharmacology and Experimental Therapeutics·Sagar AgarwalWilliam F Elmquist
Jun 25, 2010·The New England Journal of Medicine·Makoto MaemondoUNKNOWN North-East Japan Study Group
Feb 8, 2011·CA: a Cancer Journal for Clinicians·Ahmedin JemalDavid Forman
Jul 20, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Lecia V SequistJoan H Schiller
Oct 11, 2011·Molecular Cancer·Amanda J O'NeillR William G Watson
Jul 19, 2013·Molecular Cancer Therapeutics·Yezi ZhuAllen C Gao
Oct 9, 2013·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·David R SpigelAmy C Peterson

❮ Previous
Next ❯

Citations

Jun 25, 2016·International Journal of Molecular Sciences·Ming HongYibin Feng
Apr 6, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Huan-Huan ShaJi-Feng Feng
Apr 5, 2017·European Journal of Drug Metabolism and Pharmacokinetics·Ranjeet Prasad DashNuggehally R Srinivas
Mar 14, 2018·Cancer Science·Hidejiro TorigoeShinichi Toyooka
Jan 31, 2018·Future Science OA·Austin Y Shull, Christopher L Farrell
May 3, 2019·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Andrea N RobinsonMichael M Gottesman
Jul 12, 2017·Oncology Letters·Fenfei ZouAkihiko Gemma
Apr 5, 2017·Journal of the National Cancer Institute·Alexis B CortotDavid Tulasne
Aug 5, 2017·Cancers·Antoine LegrasHélène Blons
Feb 12, 2020·Journal of Experimental & Clinical Cancer Research : CR·Ninadh M D'CostaAlan I So
Jan 20, 2016·International Journal of Oncology·Nobuhiko NishijimaAkihiko Gemma
May 22, 2020·Frontiers in Cell and Developmental Biology·Xing HuangTingbo Liang
Feb 17, 2021·Signal Transduction and Targeted Therapy·He-Ming ZhouQin Li
Dec 15, 2020·Trends in Cancer·Marie-Julie NokinDavid Santamaria
Apr 20, 2021·Therapeutic Advances in Medical Oncology·Hang-Ping YaoMing-Hai Wang

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